Acetylcholine released from a cholinergic nerve in the peripheral and central nervous systems causes various biological reactions through binding with two types of acetylcholine receptors, a nicotinic receptor and a muscarinic receptor, respectively. Among these, the muscarinic receptor belongs to a seven-pass transmembrane-type G protein-conjugated receptor superfamily, and at the present time, there exist five subtypes of these receptors, M1, M2, M3, M4, and M5, which are each encoded by different gene sequences. These five types of the receptors are widely distributed in each tissue of a vertebrate body. The muscarinic receptor is known to have both the excitatory and inhibitory actions, depending on its subtype. Specifically, the functional roles of various muscarinic receptors, for example, a contribution of the M3 receptor present in the airway smooth muscle to contraction reactions of the smooth muscle, or other roles, have been reported in General Overview of Caulfield, et al. (Non-Patent Document 1).
In the lung, the muscarinic receptor is present in the tracheal and bronchial smooth muscles, the submucosal glands, and the parasympathetic ganglion. It has been known that the distribution density of the muscarinic receptors is highest in the parasympathetic ganglion, and then in the submucosal glands and the tracheal smooth muscle in this order, and is lowest in the bronchial smooth muscle (Non-Patent Document 2).
As the muscarinic receptor which plays an important role in the lung tissue, three types of M1, M2, and M3 may be mentioned. The M3 receptor which is present in the airway smooth muscle is involved in the smooth muscle contraction, which causes airway obstruction. If the M3 receptor is activated, a phospholipase C in the cytoplasm is activated through the activation of the stimulatory G protein, subsequently phosphatidylinositol 3-phosphate is dissociated into phosphatidylinositol 4,5-diphosphate, and finally a contractile protein is phosphorylated. The M3 receptor is present in the submucosal glands, in addition to in the smooth muscle which is present in the lung tissue. If this type of M3 receptor is activated the mucus is secreted.
The M2 receptors constitute about 50 to 80% of the cholinergic receptors which are present in the airway smooth muscle. Details on the role of this subtype of the receptor are still unclear, but the reduction of the amount of the cAMP's produced in the cytoplasm is believed to inhibit the relaxation of the airway smooth muscle due to the sympathetic innervation. The central M2 receptors are distributed in the postganglionic parasympathetic fibers. Under physiological conditions, the central M2 receptor plays a role in the negative regulation of the release of acetylcholine from the parasympathetic. The M2 receptor which is expressed in the cardiac muscle is due to regulation of the chronotropic action. The M1 receptor is found in the parasympathetic ganglion of the lung tissue, and functions to facilitate neurotransmission. The M1 receptors are distributed not only in the ganglion, but also in the peripheral lung parenchymal tissue, but their function is unclear.
In the lung tissues, the abnormal function of the muscarinic receptor is perceived when a large number of pathologic conditions are formed. Particularly, for an inflammatory disease such as a chronic obstructive pulmonary disease (COPD), asthma and the like, a sustained inflammatory response leads to dysfunction of an inhibitory M2 receptor which is present in a parasympathetic nerve, and increases the release of acetylcholine by vagus nerve stimulation (Non-Patent Document 3). Therefore, the dysfunction of this receptor causes the relative preference of the M3 receptor-mediated function, which leads to the induction of airway hyperreactivity. Therefore, a drug that selectively antagonizes the M3 receptor-mediated function without interfering with the M2 receptor-mediated function is thought to be an effective therapeutic agent.
COPD shows a limit in the airflow, usually by an organic change based on the persistent inflammation in the peripheral airways and primarily, the alveoli, allowing the symptoms of coughing, sputum, breathlessness and the like to be perceived, occupies the fourth leading cause of death as of the year 2005, and is a major cause of death world-wide. Further, by the year 2020, it is expected to be the third leading cause of death. Smoking is a major risk factor of COPD, and recently, in addition to this, air pollution or the like due to dust is also mentioned as a risk factor among other issues. The medical cost required for COPD treatment is very high, and the number of patients is expected to increase in future.
A therapy with an inhaled anticholinergic agent is regarded as a drug firstly chosen for the above-described diseases (Non-Patent Document 4), and in recent years, in each region in the Western countries and Asia, a long-term operating (once a day) anticholinergic agent, tiotropium bromide (Spiriva (registered trademark)), has been launched on the market. However, by taking into account the status of treatment, none of the conventional anticholinergic agents including Spiriva (registered trademark) are complete from the viewpoints of either convenience or safety, and thus, there is a room for improvement at present. Therefore, there is a strong desire to create an oral or inhaled anticholinergic agent which is improved in any of the above-described viewpoints.
For example, there has been known a carbamate compound which has an M3 receptor antagonistic action and has an airway contraction inhibitory action, wherein the Ring A of the following formula is an unsubstituted benzene or an unsubstituted pyridine (Patent Document 1). In this Patent Document, the compound of the present invention is not disclosed or suggested.

[for the symbols in the formula, refer to this publication]
Further, there has been known a carbamate compound as below, which has an M3 receptor antagonistic action and has an airway contraction inhibitory action (Patent Document 2). However, in this Patent Document, the compound of the present invention is not disclosed or suggested.

[for the symbols in the formula, refer to this publication]    [Patent Document 1] Pamphlet of International Publication No. WO 95/21820    [Patent Document 2] Pamphlet of International Publication No. WO WO95/06635    [Non-Patent Document 1] Pharmacology and Therapeutics, 1993, vol. 58, pp. 319-379    [Non-Patent Document 2] American Journal Respiratory and Critical Care Medicine, 1998, 158, pp. 154S-160S    [Non-Patent Document 3] Life Science, 1999, vol. 64 (6-7), pp. 449-455    [Non-Patent Document 4] American Journal Respiratory and Critical Care Medicine, 2001, 163, pp. 1256-1276